Late stage disease (persistent infection) occurs months to years after initial infection and may be manifested as chronic arthritis, chronic neurologic abnormalities or acrodermatitis chronica atrophicans. Not all patients with Lyme disease have this characteristic progression of symptoms. Late stage disease usually requires more intensive therapy and may result in permanent sequelae. In particular, late neurologic involvement is associated with chronic, slowly progressive disease.¹⁰

The rate of asymptomatic infection has not been well studied in adults. In the LYMErix [Lyme Disease Vaccine (Recombinant OspA)] study, the rate of asymptomatic infection (for definition, see Clinical Efficacy, Asymptomatic B. burgdorferi infection below) was approximately 0.25% per year with one case of asymptomatic infection occurring for every four cases of erythema migrans.

Late stage disease may result from early disease that is either unrecognized or fails to respond to treatment, or from asymptomatic infection. The relative importance of these conditions in predisposing to the development of late stage disease is unknown.

Diagnosis: Diagnosis is based on clinical manifestations, epidemiologic information and laboratory evaluation. Confirming the diagnosis may be difficult in some cases.

At a consensus meeting of the CDC and ASTPHLD (Association of State, Territorial and Public Health Laboratory Directors), a two-step approach was recommended if serologic evaluation of Lyme disease is required.¹¹ A sensitive screening test such as an enzymelinked immunosorbent assay (ELISA) or immunofluorescent assay (IFA) is recommended as the initial laboratory test and if positive or equivocal, immunoblot (Western blot) testing should be performed to confirm the results (see PRECAUTIONS, Laboratory Test Interactions).

LYMErix Mechanism of Action: LYMErix stimulates specific antibodies directed against B. burgdorferi. The organism contains several outer surface proteins, with lipoprotein OspA being immunodominant.¹² Administration of lipoprotein OspA to mice resulted in the formation of specific IgG anti-OspA antibodies, including those directed against a specific epitope, LA-2 (designated LA-2 equivalent antibodies). These antibodies have demonstrated bactericidal activity. Studies have shown that mice immunized with recombinant lipoprotein OspA are protected against disease after tick challenge with B. burgdorferi.¹³ LA-2 equivalent antibody titers have been shown to correlate with protection against infection in laboratory animals.¹⁴

B. burgdorferi express OspA while residing in the midgut of the infected tick, but OspA is downregulated after tick attachment and is usually undetectable or absent when B. burgdorferi is inoculated into the human host.¹⁵ Thus, a novel hypothesis has been proposed to explain the effectiveness of lipoprotein OspA vaccination: when infected ticks bite humans who have been vaccinated with LYMErix, the vaccine-induced antibodies are taken up by the tick and interact with the B. burgdorferi in the midgut of the tick, thereby preventing transmission of the organism to the host. This mechanism has been suggested by a pre-clinical study in which B. burgdorferi were detected by immunofluorescence assay in none of the ticks that fed on OspA-immunized mice, compared with 72% of ticks that fed on control-immunized mice.¹³

Clinical Efficacy

A randomized, double-blind, multicentered, placebocontrolled trial has shown that LYMErix confers protection against Lyme disease.¹⁶ This trial was conducted in highly endemic areas of the United States, primarily in the Northeast, and enrolled 10,936 subjects (5,469 vaccinees; 5,467 placebo recipients) ages 15 to 70 years. Subjects with a history of previous Lyme disease were not excluded from this trial.

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